Germ-free (GF) Sprague-Dawley (SD) and Buffalo (Buf) rats develop intestinal carcinomas in response to orally-administered 1,2 dimethylhydrazine (DMH). The tumor response to DMH was very low in GF Lobund Wistar (Lob-Wist) rats. Three levels of responses were demonstrated: SD (highest), Buf (intermediate), and Lob-Wist (lowest). The nature of the "genetic" resistance to DMH-induced intestinal tumors will be analyzed, as follows: 1. F1 hybrids of SD x Lob-Wist, SD x Buf and Lob-Wist x Buf rats, with appropriate homozygous controls, will be subjected to the DMH protocol (30 mg DMH/kg/10 weeks and 10 weeks observation and examination). 2. The fate of DMH in Lob-Wist and SD rats will be determined by assay of DMH in the intestinal tract and in liver following single and multiple feedings. This will be done (a) with H3-DMH to determine distribution patterns in relation to rat strain; (b) with recovery of DMH in intestinal contents at intervals after feeding; (c) determining bile acid levels in rats of the three strains, and (d) determining role of liver in DMH-induced intestinal carcinomatosis through liver metabolite stimulation and depression. 3. Factors involved in metastasis will be determined. 4. Possible applications of GF rats with primary colo-rectal tumors to therapeutic procedures will be initiated. We will continue propagation of GF and conventional Sprague-Dawley, Lobund Wistar, and Buffalo rats, and further characterize the latter GF strain. Rats will be made available to other investigators.